Bosentan, an Endothelin Receptor-1 Antagonist, Exerts Cardioprotective Effects During Myocardial Ischemia-Reperfusion Injury in Experimental Rats

Background and Objective: Myocardial infarction is caused by persistent ischemia with or without reperfusion. Bosentan, an endothelin receptor-1 antagonist, is primarily used to treat pulmonary arterial hypertension. However, its effect on myocardial ischemia-reperfusion injury (MIRI) has yet to be evaluated. Thus, the present investigation aimed to investigate the underlying cardioprotective mechanism of bosentan against MIRI in experimental rats. Materials and Methods: Sprague-Dawley male rats (200-220 g) were administered either vehicle, diltiazem (10 mg/kg), or bosentan (25, 50 and 100 mg/kg) for 14 days, followed by induction of MIRI by partial ligation of the left anterior descending artery subsequently with reperfusion injury. One way ANOVA was used to evaluate various biochemical, molecular and histological parameters. Results: Bosentan (50 and 100 mg/kg) significantly (p<0.05) attenuated ischemia-reperfusion injury (IRI)induced cardiac damage evidenced by improvements in electrocardiographic, hemodynamic and left ventricular function tests. Elevated serum CK-MB, LDH, AST, ALT and ALP levels were effectively decreased (p<0.05) by bosentan treatment. It also effectively reduced (p<0.05) cardiac ANP, BNP, cTn-I and significantly increased (p<0.05) cardiac ATPase enzymes (Na(+)K(+)ATPase and Ca(2+)ATPase) and HO-1 levels. Western blot analysis revealed that bosentan therapy inhibited IRI-induced up-regulated CHOP and GRP78-protein expressions. Bosentan improved the IRI-induced histological aberrations in cardiac tissue. Conclusion: The findings of the present investigation suggest that bosentan exerts its cardioprotective effects by inhibiting the CHOP and GRP78 expressions.